Morphine is the natural alkaloid which gives opium its analgesic actions. It has been known and used for centuries and still today is the standard against which new analgesics are measured. Extensive chemical modifications of morphine have produced analgesic substances of widely differing potency and addictive properties. Codeine, for example, is the methyl ethyl of morphine, and is a mild analgesic with only slight physical dependance liability. In contrast, the diacetyl derivative of morphine, heroin, is a powerful agonist with extremely high physical dependance liability. In addition to morphine and codeine, and many semisynthetic derivatives of naturally occurring opium alkaloids, there exist several structurally distinct chemical classes of drugs which display pharmacological properties related to those of morphine. Clinically useful drugs are found among the morphinans, benzomorphans, methadones, phenylpiperidines, and propionanilides.
Recently several new drugs having varied analgesic agonist and antagonist properties with varying degrees of physical dependance liabilities have been synthesized, and in some cases can be viewed as morphine part-structures. For example, certain decahydroisoquinolines having a hydroxyphenyl group attached at the ring junction para to the isoquinoline nitrogen atom can be viewed as a morphine part-structure. Such compounds are the subject of Belgian Pat. No. 802,557.
An object of this invention is to provide certain 2-substituted-5a-aryl-decahydrocyclopent[c]azepines which can be viewed as being structurally related to certain morphine part-structures such as the aforementioned morphinans, benzomorphans, and isoquinoline derivatives. The compounds provided by this invention have not heretofore been described, as no method for their preparation has been available. Additionally, the compounds of this invention display an unpredictable variation in analgesic antagonist and agonist properties, with decreased physical dependance liability.